tbuckley/cabot-search huggingface dataset:
Cabozantinib (C) in combination with atezolizumab (A) in urothelial carcinoma (UC): Results from Cohorts 3, 4, 5 of the COSMIC-021 study.
Authors: Sumanta K. Pal, Neeraj Agarwal, Parminder Singh, Andrea Necchi, Bradley Alexander McGregor, Ralph J. Hauke, Thomas Powles, Cristina Suárez, Carla M.L.- Van Herpen, Ulka N. Vaishampayan, Ramu Sudhagoni, Dominic Curran, Lana Andrianova, Yohann Loriot
Journal: Journal of Clinical Oncology (2022)

4504 Background: C, a multitargeted receptor tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment that may enhance response to immune checkpoint inhibitors (ICIs). COSMIC-021, a multicenter phase 1b study, is evaluating C + A (anti‒PD-L1 therapy) in various solid tumors (NCT03170960). C + A demonstrated encouraging clinical activity in cohort 2 of COSMIC-021 in patients (pts) with UC previously treated with platinum-containing chemotherapy (chemo) (Pal S et al. ASCO 2020. Abstract 5013). Outcomes of C + A from 3 other UC cohorts (C3, C4, C5) are presented. Methods: Pts with inoperable locally advanced/metastatic UC with transitional cell histology and ECOG PS 0‒1 were eligible. Pts enrolled in C3 and C4 had no prior therapy and were cisplatin-based chemo ineligible (C3) or eligible (C4). C5 enrolled pts with one prior ICI and no prior VEGFR-TKI therapy. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for first year and Q12W thereafter. The primary endpoint is objective response rate (ORR) per RECIST v1.1 by investigator. Other endpoints: safety, duration of response (DOR), PFS, and OS. Results: Thirty pts each were enrolled in C3 and C4, and 31 in C5. Baseline characteristics for C3, C4, and C5, respectively: median age, 74 y, 66 y, 68 y; male, 67%, 73%, 55%; ECOG PS 1, 63%, 57%, 74%; lung/liver metastasis; 33%/17%, 40%/20%, 58%/23%; ≥3 tumor sites, 30%, 43%, 45%; bladder as primary site, 67%, 70%, 71%. As of Nov 30, 2021, the median follow-up for C3, C4, and C5 was 27.9, 19.1, and 32.9 mo, respectively, with 1, 6, and 1 pts on treatment. C + A demonstrated clinical benefit across all cohorts (Table). Most common treatment-related adverse events (TRAEs) of any grade across C3, C4, and C5, respectively, were diarrhea (43%, 33%, 35%), nausea (27%, 17%, 26%), fatigue (27%, 27%, 48%), and decreased appetite (33%, 27%, 39%); grade 3/4 TRAEs occurred in 63%, 43%, and 45%, and there was no grade 5 TRAE. Conclusions: C + A demonstrated encouraging clinical activity with manageable toxicity in inoperable locally advanced/metastatic UC as first-line systemic therapy in cisplatin-based chemo eligible/ineligible pts and as second- or later line in pts who received prior ICI. Clinical trial information: NCT03170960. [Table: see text]
A prospective study of chemoradiotherapy for patients with locoregionally advanced penile carcinoma: Safety, efficacy and the role of HPV-status on treatment response
Authors: H-M. De Vries, S.R. Ottenhof, B. Doodeman, G.L. Vrijenhoek, V. Van Der Noort, J.M. De Feijter, E. Schaake, S. Horenblas, L. Moonen, O.R. Brouwer, M.S. Van Der Heijden, F. Pos
Journal: European Urology (2022)
Impact of positive vascular margins status after surgical resection of non-metastatic renal cell carcinoma with caval tumour thrombus: A propensity score multicentre study
Authors: N. Vamour, A. Gasmi, X. Leroy, P. Puech, M. Koussa, A. Villers, J-C. Fantoni, N. Doumerc, K. Bensalah, J. Olivier, Z-E. Khene
Journal: European Urology (2022)
Immuno- versus chemo-therapy as first line treatment for advanced urothelial cancer: A systematic review and meta-analysis
Authors: A. Martini, D. Raggi, G. Fallara, L. Nocera, F. Belladelli, L. Marandino, A. Salonia, A. Briganti, F. Montorsi, T. Powles, A. Necchi
Journal: European Urology (2022)
Transperineal fusion biopsies and target fusion cryoablation under local anesthesia in a clinical office-setting
Authors: F. Bianco, E. Luna, A. Lopez, E. Gheiler, A. Kaufman, F. Shafizadeh, M. Zachareas, J. Martinez-Salamanca, E. Gloria, M. Kattan
Journal: European Urology (2022)
Central nervous system efficacy of furmonertinib versus gefitinib in patients with non–small cell lung cancer with epidermal growth factor receptor mutations: Results from FURLONG study.
Authors: Gongyan Chen, Xiang Wang, Yunpeng Liu, Lin Wu, Yanrong Hao, Chunling Liu, Shuyang Zhu, Xiaodong Zhang, Yuping Li, Jiwei Liu, Lejie Cao, Ying Cheng, Hui Zhao, Shucai Zhang, Aimin Zang, Jiuwei Cui, Jian Feng, Fei Liu, Chuan Gu, Yuankai Shi
Journal: Journal of Clinical Oncology (2022)

9101 Background: Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with central nervous system (CNS) penetration. Here we report the CNS response to furmonertinib versus gefitinib as first-line therapy in EGFR-mutated non-small cell lung cancer (NSCLC) patients in the FURLONG study. Methods: FURLONG was a randomized, double-blind, multi-center phase III study. Patients were randomized 1:1 to receive first-line furmonertinib 80mg/d or gefitinib 250mg/d. Brain scan was mandatory at screening. Patients with asymptomatic CNS metastases who did not require steroid treatment for 28 days or more were enrolled. A pre-planned CNS efficacy analysis was done using RECIST v1.1 in patients with measurable or non-measurable CNS lesions (cFAS) and patients with only measurable CNS lesions (cEFR). Results: Of 358 enrolled patients in the FURLONG study, 133 (37%) patients were defined as cFAS and 60 (17%) were defined as cEFR according to baseline brain scan judged by a blinded independent review committee (IRC). At the cut-off date of Sep 15, 2021, CNS progression-free survival (PFS) assessed by IRC in the cFAS population was significantly longer in the furmonertinib group than in the gefitinib group (20.8 vs 9.8 months, HR 0.40 [95% 0.23-0.71]; p = 0.0011). CNS PFS rate at 6, 12, 18 months were 91%, 77%, 63% in the furmonertinib group, and 76%, 46%, 34% in the gefitinib group. In the cEFR set, confirmed CNS objective response rate was 91% in patients with furmonertinib and 65% in patients with gefitinib (p = 0.0277), and CNS disease control rate were 100% vs 84% (p = 0.9420), respectively. The mean best percentage change in the sum of target CNS lesion size from baseline in cEFR was -61.8% in the furmonertinib group versus -38.7% in the gefitinib group (p = 0.0011). Conclusions: Furmonertinib showed CNS efficacy as first-line therapy in EGFR-mutated NSCLC patients with CNS lesions. Patients treated with furmonertinib had a reduced risk of CNS progression or death, a higher CNS ORR and a deeper CNS response compared with gefitinib. Clinical trial information: NCT03787992.
The risk of recurrence in cN1 prostate cancer patients treated with radical prostatectomy varies according to preoperative staging. A comparison between 68Ga-PSMA-PET versus conventional imaging in a large, multi-institutional study
Authors: G. Sorce, G. Rosiello, G. Gandaglia, A. Stabile, D. Robesti, S. Scuderi, E. Mazzone, A. Pellegrino, A. Martini, R. Leni, L. Dambrosio, M. Picozzi, M. Tutolo, A. Gallina, N. Fossati, L. Bianchi, R. Schiavina, B. Vansevenant, G. Devos, J. Karnes, S. Joniau, F. Montorsi, A. Briganti
Journal: European Urology (2022)
RARE-20. Retrospective analysis of 9 pineoblastoma
Authors: Ruyu Ai, Juan Li, Mingyao Lai, Linbo Cai
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pineoblastomas (PBs) are rare, supratentorial, primitive neuroectodermal tumors. Little is known with the clinical features and outcomes of PBs. METHODS: We retrospectively analyzed consecutive patients with PBs who were treated in Guangdong Sanjiu Brain Hospital between December 2006 to May 2020. RESULTS: A total of 9 patients (7 males and 2 females) with PBs were treated in our hospital with a median age of 9 yrs (range: 1-36 yrs) at diagnosis. Total or near-total resection was achieved in 3 patients (33%), partially resection in 4 (44.4%),and biopsy in 2(22.2%). There were 4 patients have spinal cord metastasis at diagnosis. Five patients received craniospinal irradiation (CSI), with concurrent or adjuvant chemotherapy. The average total dose of CSI was 34.80±2.683Gy, and the average dose to local tumor bed was 56.08±6.41Gy. Two patients younger than 3 years old only received chemotherapy, while 1 patient did not receive any postoperative treatment, and 1 patients was unknown. The median followed up time is ? months(range:3-39 months). At the last follow up, 5 patients were died, 3 patients were survived, and 1 was lost to follow-up. The median OS was 31 months (95%CI 1.782-60.281). Disease progression occurred in 5 patients during the follow-up period, and the median PFS was 19 months. CONCLUSION: Pineoblastoma is a rare central nervous system malignancy with a tendency for disseminated disease. Comprehensive therapies such as surgical resection, radiation and chemo therapy are effective therapies for PBs.
Double jeopardy? A closer look at cancer histories of individuals with multiple germline pathogenic variants.
Authors: Carolyn Horton, Min-Tzu Lo, Amal Yussuf, Colin Young, Cassidy Carraway, Nihat Bugra Agaoglu, Brittany L. Bychkovsky, Huma Q. Rana
Journal: Journal of Clinical Oncology (2022)

10514 Background: Germline multigene panel testing has led to the increased detection of multiple co-occurring pathogenic variants (PV) in the same individual. As this occurrence is still relatively rare, reports of these individuals have been limited. Therefore, we sought to describe the clinical features of individuals with multiple PV identified at a single high-volume diagnostic laboratory. Methods: We performed a retrospective review of demographics and clinical data for individuals with &gt; 1 pathogenic or likely pathogenic variant (PV) who underwent hereditary cancer panel testing (5-67 genes) between May 2012 and April 2017. In recessive genes (i.e. MUTYH), PV were only included when biallelic. PVs with reduced penetrance ( APC p.I1307K; CHEK2 p.I157T, p.S428F, p.T476M) were excluded. In individuals with the most common combinations of genes, personal cancer history and age at cancer diagnosis was evaluated. Results: A total of 555 individuals were identified with multiple PVs. Most individuals were female (85.1%), had a personal history of cancer (73.3%) and 26.3% had two or more primary cancers. CHEK2 was most often seen in co-occurrence with a PV in a different gene (137 observations), followed by ATM (120 observations), BRCA2 (110 observations), and BRCA1 (88 observations). Among cases in which clinical information was provided (n = 545), the five most frequent co-occurring combinations were in ATM/CHEK2 (25), ATM/BRCA2 (23), BRCA1/CHEK2 (19), CHEK2/CHEK2 (16), and BRCA2/CHEK2 (14). Individuals with co-occurring PVs in CHEK2/CHEK2 had the youngest age at first cancer diagnosis (mean = 41.5y; median = 42y), the highest rate of breast cancer diagnoses and other cancer diagnoses (100.0% and 70.6% of individuals, respectively), and the highest proportion of individuals with &gt; 1 primary cancer (52.9%). Conclusions: Our results indicate that individuals with two PVs in CHEK2 have an average age of cancer onset that is similar to individuals with either a BRCA1 or BRCA2 concurrent PV. Additionally, individuals with two PVs in CHEK2 were more likely to have multiple primary cancers as compared to others in the cohort with concurrent PVs including those with either a BRCA1 or BRCA2 concurrent PV (Table). Continued studies, including comparisons to individuals with one PV, will provide valuable insight to aid in counseling and management of individuals with multiple germline PV. [Table: see text]
Outcomes Among Patients With 1-Year Survival After Intensive Care Unit Treatment for COVID-19
Authors: Wei Bai, Todd Jackson, Yu-Tao Xiang
Journal: JAMA (2022)

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LGG-42. Thromboembolic toxicity observed with concurrent trametinib and lenalidomide therapy
Authors: Priya Chan, Ashley Sabus, Molly Hemenway, Kathryn Chatfield, Nicholas Foreman, Nathan Dahl
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Event-free survival of pediatric low-grade glioma (pLGG) is poor, and patients often require multiple treatment strategies. The hallmark of pLGGs are genetic aberrations of the mitogen-activated protein kinase pathway, which lead to constitutive pathway activation. MEK and RAF inhibitors target this pathway and are efficacious in early phase trials in recurrent pLGGs. However, not all patients respond to monotherapy, and many experience progression after completion of therapy. Evaluating combination therapies that may enhance efficacy or prolong disease stabilization is warranted. Lenalidomide is an immunomodulatory agent with an anti-tumor effect demonstrated in phase 1 trials in recurrent pediatric central nervous system (CNS) tumors. OBJECTIVE: To describe our institutional experience using concurrent trametinib and lenalidomide in the treatment of primary pediatric central and peripheral nervous system (PNS) tumors. METHODS: Retrospective review of patients’ medical records. RESULTS: Four patients with locally recurrent primary CNS or PNS tumors, three with WHO grade II pilomyxoid astrocytomas and one with a plexiform neurofibroma, were treated with trametinib and lenalidomide concurrently. Two patients developed severe thromboembolic events. One patient was treated with combination therapy for seven months until trametinib and lenalidomide were held after urgent ventriculoperitoneal shunt revision. Shortly following shunt revision, he experienced near-complete vision loss. MRI of the brain demonstrated a left posterior watershed territory hypoxic-ischemic injury. In a second patient, after four months of combination therapy, surveillance echocardiogram showed an incidental finding of severe biventricular dysfunction with a left ventricular ejection fraction (LVEF) of 17.7% and two mural thrombi in the left ventricular apex. She started losartan and enoxaparin and discontinued trametinib and lenalidomide. Her LVEF normalized four months later, and the mural thrombi resolved. CONCLUSIONS: Given the severe thromboembolic events experienced by these patients treated with concomitant trametinib and lenalidomide, this combination requires further investigation, and we urge caution if used concurrently.
The effect of advances in epithelial ovarian cancer treatment on population mortality.
Authors: Aifen Wang, Qing Ye, Jinghuan Lv, Weidong Hu, Ninghan Feng, Shunyu Hou
Journal: Journal of Clinical Oncology (2022)

5540 Background: Epithelial ovarian carcinoma is the most common and progressive subtype of ovarian cancer. Mortality trends based on race remains unclear. Methods: SEER was used to assess epithelial ovarian cancer mortality and relevant deaths from epithelial ovarian cancer to incident cases. Population-level mortality trends were evaluated according to specific causes. In addition, epithelial ovarian cancer incidence and survival was assessed according to calendar year and race. We applied Joinpoint software to evaluate trends in incidence or incidence-based mortality. Results: Age-adjusted incidence of white patients was the highest, followed by Asians and Black patients. Incidence-based mortality of Asian patients was the lowest among all patients, followed by White and Black patients. Incidence-based mortality of all causes of death of epithelial ovarian cancer increased sharply by 65.09% annually from 2000 through 2002, then rose gradually by 9.45% annually from 2002 through 2005, and then increased more slowly annually from 2005 through 2018. Other causes of death of incidence-based mortality displayed similar trends. However, incidence-based mortality of specific ovarian epithelial cancer deaths displayed an annual decrease of 0.08% from 2005 through 2018, following a sharp annual increase of 65.68% from 2000 through 2002 and 6.55% from 2002 through 2005. White patients with epithelial ovarian cancer showed the highest 2-year relative survival, followed by Asians, Black patients and Native Americans, with all patients showing an improved survival rate. Among White patients with epithelial ovarian cancer, incidence increased annually by 1.98% from 2000 through 2011 and then flattened out to an annual increase of 0.03%. Incidence-based mortality of White patients increased sharply by 56.70% annually from 2000 through 2002, then increased slowly by 7.90% annually from 2002 through 2005, and 2.00% annually from 2005 through 2018. Among Asian patients with epithelial ovarian cancer, incidence increased at an annual rate of 2.39% from 2000 through 2018. Incidence-based mortality of Asian patients increased steeply by 78.70% annually from 2000 through 2002, then slowed down to an annual rate of 2.50% from 2002 through 2018. Among Black patients with epithelial ovarian cancer, incidence increased annually by 10.83% from 2000 through 2002 and 2.43% from 2006 through 2016 and declined annually by 0.82% from 2002 through 2006 and by 1.82% from 2016 through 2018. Incidence-based mortality of Black patients displayed a sharp annual increase of 63.70% from 2000 through 2002, then slowed to an annual rate of 1.90% from 2002 through 2018. Conclusions: Incidence-based mortality of specific ovarian epithelial cancer death decreased annually from 2005 through 2018. These results may be related to treatment advances of epithelial ovarian carcinoma, particularly surgical strategy and chemotherapy.
The mortality of venous thromboembolism in hospitalized patients with different gastrointestinal malignancies.
Authors: Zainab Fatima, Mohammad Darweesh, Ammar Alhabhbeh, Nayef Hikmat Abdel-Razeq, Sukesh Manthri, Mark Young
Journal: Journal of Clinical Oncology (2022)

e16036 Background: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in cancer patients. Our study compares the mortality in hospitalized VTE patients among the five most common Gastrointestinal (GI) malignancies which includes esophageal, gastric, pancreatic, colorectal, and hepatobiliary cancers. Methods: A retrospective study was conducted utilizing the Nationwide Inpatient Sample database (NIS) from 2016 to 2018. Patients with Venous thromboembolism (VTE) were identified using ICD 10 codes from all primary discharge diagnoses. Only deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered. Patients with VTE were further divided into groups: esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer, hepatobiliary cancer, and compared with patients who did not have these malignancies. Patients younger than 18 years of age or patients with missing age, gender or race were excluded. Among the hospitalized patients with VTE, we investigated the difference in mortality with different gastrointestinal malignancies. Adjusted odds ratio (OR) was calculated using multivariate regression analysis. Results: Among 751,834 patients discharged with a VTE diagnosis, 0.24% had esophageal cancer, 0.25% had gastric cancer, 0.93% had pancreatic cancer, 1.10% had colorectal cancer, 0.35% had hepatobiliary cancer, and the other 97.14% did not have these malignancies. The study shows that adults admitted to the hospitals for VTE have higher mortality when compared to patients who did not have GI malignancies, with esophageal cancer having the highest inpatient mortality with an OR of 2.66 (95% CI 1.78-3.94, P of 0.00). For the remaining GI cancers, gastric cancer had an OR of 1.74 (95% CI 1.141-2.661, P of 0.010), pancreatic cancer had an OR of 1.74 (95% CI 1.402-2.178 P of 0.000), hepatobiliary cancer had an OR of 1.67 (95% CI 1.144-2.439 P-value of 0.002) and colorectal cancer had OR of 1.18 (95% CI 0.930-1.517 P of 0.169), which was not statistically significant. Conclusions: Pancreatic and gastric cancers have a higher risk of VTE and frequently score high in validated VTE risk assessment tools such as the Khorana score. This study shows that VTE in hospitalized patients with esophageal cancer is associated with greater mortality. More research is needed to analyze the outcomes of VTE in cancer patients and to identify those who would benefit from thromboprophylaxis. Due to the nature of the NIS database, one of the study's limitations was the difficulty in identifying patients receiving DVT prophylaxis.
Evaluation of Lynch syndrome risk models in a multicenter diverse population.
Authors: Jenny Lu, Stephen Knapp, Gubidxa Gutierrez Seymour, Cathy Wang, Theodore Huang, Jane Liang, Kai Yang, Danielle Castillo, Josef Herzog, Giovanni Parmigiani, Stephen B. Gruber, Danielle Braun, Gregory Idos
Journal: Journal of Clinical Oncology (2022)

10597 Background: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC) with an increased CRC lifetime risk of 70-80%. LS affects 1:250 individuals and is caused by pathogenic variants in the mismatch repair (MMR) genes. Statistical prediction models such as MMRpro and PREMM5 are widely used to identify LS carriers. However, these models are trained and validated in mostly white populations, and there remains a gap in understanding their performance in Hispanic populations. The purpose of this study was to evaluate the performance of MMRpro and PREMM5 on a large Hispanic cohort from the Clinical Cancer Genomics Community Research Network (CCGCRN). Methods: We validated MMRpro and PREMM5 on 3,490 CCGCRN families, of which 1,122 are Hispanic and 2,062 Non-Hispanic. The two models were evaluated for discrimination using the C-statistic, calibration using the observed to expected ratio (O/E), and overall performance using the root Brier score and negative and positive predictive value (NPV/PPV) at the 5% carrier probability threshold. Evaluations were stratified by ethnicity, and 95% confidence intervals were obtained via bootstrapping for all measures. Results: The C-statistic is 0.90 for both MMRpro (95% CI: 0.88, 0.92) and PREMM5 (95% CI: 0.87, 0.92). When stratified by ethnicity, the C-statistics are 0.96 (95% CI: 0.94, 0.97) and 0.86 (95% CI: 0.83, 0.89) for Hispanics and Non-Hispanics, respectively, in MMRpro, and 0.96 (95% CI: 0.94, 0.97) and 0.84 (95% CI: 0.79, 0.88) in PREMM5. Both models underpredict mutation probabilities, with O/E ratios ranging from 1.79 to 1.96. At a 5% threshold, variations in PPV between Hispanics and Non-Hispanics are observed in both models: 0.72 (95% CI: 0.63, 0.80) and 0.43 (95% CI: 0.37, 0.50) in Hispanic and Non-Hispanic groups in MMRpro; 0.50 (95% CI: 0.43, 0.57) and 0.25 (95% CI: 0.20, 0.30) in PREMM5. We observe less variation and higher values in NPVs in both models. Conclusions: Overall, MMRpro and PREMM5 perform well in this cohort in predicting the probability of having a pathogenic variant in an MMR gene, with modest underprediction. While these results offer reassurance for the clinical use of MMRpro and PREMM5 in Hispanic populations, further validation studies in underrepresented racial and ethnic populations are crucial.